Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/70023
Title: Adult-onset Alexander disease with a heterozygous D128N GFAP mutation: A pathological study
Authors: Cabrera-Galván, Juan José 
Martínez-Martin, María Soledad 
Déniz-García, Daniel
Araujo-Ruano, Eduardo
Travieso-Aja, María Del Mar
UNESCO Clasification: 3207 Patología
Keywords: Alexander Disease
D128N Gfap Mutation
Immunohistochemistry
Mri
Pathology
Issue Date: 2019
Journal: Histology and Histopathology 
Abstract: The various forms of Alexander disease (AD) have been linked to heterozygous point mutations in the coding region of the Human glial fibrillary acidic protein (GFAP) gene. The aim of this study was to confirm and characterise an adult variant of AD based on the presence of Rosenthal fibres, which were identified at brain autopsy. We performed histological and immunohistochemical studies and mutation screening by cycle sequencing of exons 1, 4, 6, and 8. A heterozygous D128N GFAP mutation, previously described in three other cases of adult-onset AD (AOAD), was genetically confirmed. The mutation was seemingly sporadic. Symptoms of the female, 65-year-old patient started with occasionally asymmetric motor impairment and concluded, 23 months later, with a lack of spontaneous movement in all four limbs, reduced consciousness, an acute respiratory problem, and eventually lethal exitus. The most striking characteristics were a cerebellar syndrome with subsequent clinical signs due to brainstem and spinal cord involvement. The final diagnosis was based on a complete autopsy, detection of Rosenthal fibres, GFAP, vimentin, alpha B-crystallin, ubiquitin, hsp27, neurofilament, and synaptophysin, and the identification of the corresponding GFAP gene mutation. Blood analyses were positive for ANA and rheumatoid factor. In conclusion, this work describes sporadic, rapidly advancing AOAD in a female patient and links it with other published cases with the same mutation. Reflections are provided on the influence of vasculitis and ANA in AD as well as the presence of Rosenthal fibres in the neurohypophysis.
URI: http://hdl.handle.net/10553/70023
ISSN: 0213-3911
DOI: 10.14670/HH-18-110
Source: Histology and Histopathology [ISSN 0213-3911],v. 34 (9), p. 1073-1088
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